Professor Thomas Mellman and Research Team Examine Sleep Deprivation and Trauma Memory

Thomas A. Mellman, M.D., professor of psychiatry and behavioral sciences and director, Center for Clinical and Translational Research and Stress/Sleep Studies Program, along with his colleagues in the College of Medicine, recently shared with Dr. Gwen Bethea, HUGS editor, their research that he hopes will enhance recognition of the relationship of sleep deprivation and trauma memory.

Q:You and researchers Dr. Tyish Hall Brown and Dr. Ihori Kobayashi who are part of the Sleep Stress Research Program of the Department of Psychiatry and Behavioral Sciences in the Howard University College of Medicine, were recently awarded a $275,000 grant from NIH to study "Sleep and Processing Traumatic Memory." Could you share some of the major findings thus far of this research? Mellman: That grant was about evaluating sleep's role in adaptive emotional processing (i.e. recovery). Main findings were published: Kobayashi I,* Mellman TA,* (* equal authorship) Altee D., Howell MK, & Lavela J. (2016) Sleep and Processing Trauma Memories. Journal of Traumatic Stress. 29:568-57.

The following abstract summarizes that study.

Sleep has been implicated in learning that is key to adaptive processing of trauma memories. Experimental studies that have demonstrated sleep's involvement in trauma memory processing in humans have utilized analogues of trauma for stimuli. The present study evaluated relationships between sleep and adaptive emotional processing of trauma memories following written narrative exposure (WNE) to traumatic events experienced by participants with clinically significant PTSD symptoms. Twenty-one urban-residing non-treatment-seeking adults with full or subthreshold symptoms of PTSD completed four sessions of 30-minutes WNE with the first session either in the evening or the morning. There was a significant reduction of PTSD symptom severity after the four WNE sessions, but there was no interaction between group assignment based on the initial session's proximity to sleep and initial or total reduction of PTSD symptom severity. Polysomnography following evening WNE revealed increased duration of total sleep and N2 minutes and percent, reduced N3 percent, and increased eye movement density during rapid-eye-movement (REM) sleep compared with baseline recordings. Reduced N3 percent and increased REM density were associated with less improvement of PTSD symptoms. These findings suggest a relationship between preservation of diminished arousal during sleep and adaptive trauma memory processing.

Q:What are the major findings of your second grant, "Sleep Adaptations to Stressful Environments," for $275, 000 awarded in April 2012 by the National Institute of Minority Health and Health Disparities? Mellman: Sixty-four (39 female) individuals of whom 34 received monitoring in their homes, participated in evaluations, which included actigraphy, polysomnography, and voice recordings eliciting pre-sleep cognitions and behaviors. We investigated the relationship between a variable-number tandem-repeat (VNTR) Period 3 gene (PER3) polymorphism and sleep adaptation to stressful urban environments. Seventy-five (49 female) African American participants (ages 18 - 35 years) living in neighborhoods with high rates of violent crime were selected for the study based on converging criteria for good or poor sleep. Categorization of sleep quality was based on the Insomnia Severity Index (ISI) estimates of typical sleep duration and sleep efficiency. Other assessments included the Fear of Sleep Index (FOSI) and City Stress Inventory (CSI). Whole blood DNA was analyzed for the 4 and 5 VNTR alleles using polymerase chain reaction (PCR) and restrictive enzyme digestion. Fifty-seven per cent of those who were homo- or heterozygous for the 4-repeat allele were poor sleepers versus 25% of those homozygous for the 5-repeat allele; v2 = 4.17, P = 0.041. In a logistic regression model with all the variables with significant bivariate relationships to sleep quality group, FOSI was the only significant predictor (v2 = 5.68, P = 0.017). FOSI scores were higher among those with the 4-repeat allele (t = 2.66, P = 0.013). The PER3 4 and 5 VNTR polymorphisms appear to influence sensitivity to the effects of stressful urban environments on sleep. While FOSI was the only variable associated independently with sleep quality category, the candidate vulnerability allele was also associated with greater 'fear of sleep'.

We initially determined that the overall subject pool, on average, lived in predominantly African-American neighborhoods with rates for violent crime that were 2 -3 times higher than national averages. There was a trend for the poor sleepers to have provided higher ratings for neighborhood stress (p < .06) than those designated as good sleepers; however, census derived rates of violent crime and poverty were similar between the groups. Poor sleepers, however, endorsed items on the Fear of Sleep Index that were more than 3X higher than the good sleepers (p < .001).

Comparisons between objective sleep recordings done in the home environment versus the clinical research unit sleep laboratory tended to corroborate the notion primarily from the PTSD sleep literature that participants can be conditioned to sleep more poorly in their home environments. Total sleep durations were greater in the laboratory (p < .05) and measures of wake after sleep onset were numerically greater in the home environment.

Finally, we applied qualitative analysis to digital voice recordings from pre-sleep periods in the home environment as a means of identifying cognitions and behaviors that contribute to pre-sleep arousal and interfere with sleep. By far, the most common, and somewhat over-represented in the poor sleeper group, was use of electronic devices (television, phones, computers) while in bed. In some cases this was explicitly used as a distraction from concerns regarding environmental safety. Poor sleepers were also more likely to report being distracted by noises from outside of the home. We distinguished thoughts related to anticipation (e.g., planning, or envisioning the next day) from worries which could focus on a variety of topics, including finances, consequences of sleep loss, as well as safety.
The grant awarded this year is Sleep Stress and Cardiovascular Health for just over $2 million over five years.

Here is the abstract summarizing the project for which we recently began collecting data:

Distressed neighborhood environments, posttraumatic stress, and compromised sleep are inter-related problems that have all been implicated in the health disparities affecting urban minorities. In our recent work, we found significant relationships between self-reported and census-derived indices of neighborhood disorder, and self-reported, habitual wake after sleep onset (WASO), with diminished nocturnal blood pressure (BP) dipping, which is a well-established risk factor for adverse cardiovascular outcomes and is over represented among African Americans. In addition to reduction of BP, there is normally a shift toward parasympathetic dominance of the autonomic nervous system (ANS) during sleep and evidence suggests that such shifts are important for healthy cardiovascular homeostasis. Our preliminary findings indicate that this shift can be compromised with PTSD and nocturnal vigilance in stressful neighborhood environments.
The goal for the proposed study is to further establish and extend a model where trauma exposure and threatening environments elicit nocturnal vigilance and sleep-related fears that compromise the healthy reduction of SNS and rise in PNS activity during sleep which in turn stimulates secretion of atherogenic humoral factors, arterial stiffening, and cardiovascular disease risk. We will examine the roles of pre-sleep cognition using a questionnaire and real time assessment, and modifiable strategies for coping with sleep disruptive cognitions. We will then evaluate the impact of providing personalized feedback and recommendations based on study observations on how participants cope with potentially sleep disruptive cognitions and sleep efficiency. We will also determine whether healthier sleep-related behaviors (however achieved) will influence changes in ANS balance during sleep and cardiovascular risk biomarkers. Thus, study findings will confirm and reveal biomarkers of cardiovascular pathogenesis related to stress and sleep disruption that precede diagnosable illness, identify targets for preventive interventions, and provide evaluation of a brief intervention that can be scaled up or built upon as study findings indicate.

Q:When and how did you come to the hypothesis that people in high crime and lo income areas might be susceptible to sleep deprivations caused by their threatening environment and how these deprivations might be affecting them?Mellman: I had formulated similar hypotheses in my work with veterans of military combat. Others have noted (see ProPublica Feb 2014) and I have also noted similarities between the effects of being in a combat zone and living in a stressful urban environment.

Q:I note that you are leading the studies, along with Dr. Tyish Hall Brown and Dr. Ihori Kobayashi in the Sleep Stress Research Program of the Department of Psychiatry and Behavioral Sciences in the Howard University College of Medicine. Would you explain the goals of the program? How long has it existed? Can members of the general public avail themselves of its services?Mellman: We started establishing the Sleep Stress Research Program shortly after my arrival in January 2004. We received an important grant to establish the program -- Nocturnal Blood Pressure and PTSD in Young Adult African Americans -- from NHLBI in 2008. Our program mission is to elucidate mechanisms by which sleep contributes to the development of, or resilience to, (mental and physical) stress-related disorders & to translate findings into clinical and preventive interventions.

Q:How are students involved in the research? Mellman: Graduate students have had important roles as study coordinators. Students have volunteered and some were subsequently employed as research assistants. A number of students have presented their findings from working with us at Howard Research Day and other venues. Several students have conducted their doctoral dissertation projects in collaboration with our program. There are students who have also volunteered as research subject participants.

Q:How is the Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS) involved in the research? Mellman: It provides critical infrastructure, e.g., the clinical research unit; and technical services.

Q:When do you expect to complete your current research in this area? Mellman: I hope it goes on forever.

Q:Can you provide the names of journals in which the results might appear? Mellman: We have published results in the Journal of Traumatic Stress; SLEEP, Journal of Sleep Research; Annals of Behavioral Medicine; and Sleep Behavioral Medicine.

Q:How do you plan to disseminate the information to affected populations? Mellman: We have presented at community forums sponsored by the aforementioned GHUCCTS.

Q:What do you envision as the long-term results of your research? Mellman: Enhancing recognition of the adverse impact to physical and mental health from the effect of threatening environments on sleep and strategies for ameliorating and overcoming them through both public education and clinical intervention.

Bethea: Thank you.

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Issue 019

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